The objective of the proposed research is to characterize, descriptively and mechanistically, the ventilatory responses to acute and chronic brain hypoxia in awake and sleeping animals. The mechanisms to be studied are those related to distribution of regional brain blood flow and regional brain oxidative metabolism. Work is to be done with three general preparations: 1) The ventilatory responses to extra-corporeal perfusion of the brains of awake goats with hypoxic blood will be studied. Time course of responses during constant flow and constant pressure perfusion will provide data concerning the role played by the brain blood flow response to hypoxia in the dynamic characteristics of the ventilatory response of hypoxia. A series of interventions (e.g., beta-adrenergic blockade) are planned to assess the other determinants of the ventilatory response to brain hypoxia. 2) The ventilatory responses of awake and sleeping (NREM and REM) cats to brain hypoxia produced by inhalation of carbon monoxide, anemia plus hypoxic and hypoxic hypoxia following peripheral chemodenervation will be determined. Additional studies will assess interaction of sleep and brain hypoxia with mofification of responsiveness to CO2 and mechanical loading of the respiratory system. 3) The distribution of brain blood flow and oxidative metabolism will be studied in awake cats. In these studies we will test a series of hypotheses concerning the role played by variations in regional (primarily cortex, diencephalon and medulla) blood flow and metabolism in setting the point of respiratory depression during progressive acute hypoxia and in the phenomena of acclimatization and deacclimatization to chronic hypoxia.